Current opinion in rheumatology最新文献

Purpose of review: Psoriatic arthritis is an immune-mediated disease that primarily affects the skin and joints. It falls under the umbrella term of rheumatic diseases, which describes a group of closely related yet distinct disorders with many common underlying molecular pathways. Despite the distinct clinical manifestation of each disorder, the shared therapeutic strategies attest to the commonality of cellular and molecular underpinnings. Herein we provide a concise yet comprehensive overview of the interleukin (IL)-23/IL-17 axis and its involvement in mechanistic pathways leading to the pathogenesis of this dual skin and joint clinical manifestation which is characteristic of psoriatic arthritis and other rheumatic diseases.

Recent findings: The interconnection between activated innate immune cells and adaptive immunity has transformed current thinking to include other organs such as the bone marrow as potential tissue of disease origin. A plethora of animal models and genetic studies converge on the critical role of IL-23/IL-17 axis, and highlight the importance of myeloid cell activation as common pathways between autoinflammatory and autoimmune diseases and chronic inflammation. These findings underscore the intricate immune mechanisms involved in inflammatory arthritis and highlight molecular mechanisms in disease pathogenesis.

Summary: These insights pave the way for the development of novel diagnostic and therapeutic strategies, with a focus on translating these findings into improved clinical practice.

Purpose of review: VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) was first described in 2020, where in a cohort of adults with unexplained fever or inflammation, systematic genetic testing was performed and 25 men with a median age of 64 years and somatic mutations in the UBA1 gene were identified. In the current review, we aim to discuss the relevant literature from January 2023 until July 2024 to give new insights into the pathophysiology, epidemiology, diagnosis and treatment of VEXAS.

Recent findings: VEXAS affects 1 : 4269 in men over the age of 50. Janus-Kinase-inhibitors (JAKi) and IL-6-inhibitors are more effective immunosuppressants against hyperinflammation. Ruxolitinib is more effective than other JAKi. Azacitidine induces remission in many patients, but only few MDS-associated patients were treated. Allogeneic stem cell transplantation is feasible for selected cases. Infections are the major cause of death. Prognosis is still poor with a 5-year mortality rate of 18-40%.

Summary: In the current review, we discuss the novelties for VEXAS, including pathogenic pathways, epidemiological data, diagnostic criteria and algorithms, treatment options and complications. We hope that this review may improve rheumatologists understanding of VEXAS. We strongly recommend enrolling VEXAS patients in registries and clinical trials, to improve prognosis of VEXAS in the future.

Purpose of review: Updates from large, observational cohorts and new statistical techniques have resulted in new data on the epidemiology of systemic sclerosis (SSc). This scoping review uses data from 2018 to 2024 to describe the current understanding of the epidemiology of SSc and several of its organ- manifestations.

Recent findings: Our review identified new estimates for the global incidence and prevalence of SSc (1.4-8.6 per 100 000 person-years and 17.6-18.9 per 100 000 individuals, respectively). Mortality rates remain high, though mortality at younger ages has decreased. interstitial lung disease and pulmonary arterial hypertension remain the most common causes of death for patients with SSc. Literature on gastrointestinal (GI) manifestations of SSc was scarce, and we identified significant heterogeneity in results. Furthermore, data on the epidemiology of racial, ethnic and sex-based disparities was lacking.

Summary: New techniques for the evaluation of the epidemiology of SSc highlight the high morbidity and mortality of SSc, and a growing prevalence rate compared with prior eras. Further research is needed to address notable heterogeneity in the reporting of epidemiological data and understudied disease manifestations, including GI disease and health disparities in disease outcomes.

Purpose of review: This review provides an update on the rapidly growing field of engineered cellular therapies for autoimmune disorders, primarily focusing on clinical experience and correlative studies with chimeric antigen receptor (CAR) T-cells.

Recent findings: To date, two case series describing treatment with CAR T-cell therapy for systemic lupus erythematosus (SLE) suggest that drug-free remission can be sustained in patients with previously treatment-refractory disease. The outcomes of these studies are similar, despite the use of different CAR constructs and lymphodepletion regimens. Although it is not yet clear whether the patients described have truly been cured, the majority of remissions have remained durable up to last follow-up at 1-2 years from treatment. Meanwhile, mechanistic studies are providing a window into how transient B-cell depletion mediates lasting benefit. With the encouraging data in SLE, CAR T-cells and other novel B-cell-depleting agents (e.g. bispecific T-cell engagers) are now being evaluated as treatment for other autoimmune conditions, with the goal of durable response.

Summary: Recent reports highlight cellular therapies as a promising strategy for patients with treatment-refractory autoimmune conditions; however, there is still limited experience, and better insight into this therapeutic approach is expected to emerge rapidly.

Purpose of review: To review recent advances in our understanding of the epidemiology, pathophysiology, and management of inclusion body myositis (IBM).

Recent findings: Recent epidemiologic studies have highlighted the morbidity and mortality associated with IBM, including the impact of dysphagia. Multiomic analyses of IBM tissues have identified new pathogenic pathways and biomarkers for use in clinical trials. New diagnostic criteria and outcome measures have been proposed to improve clinical trial design. Ongoing clinical trials are targeting T cells and autophagy.

Summary: Improvements in our understanding of IBM pathogenesis are identifying new pathways and biomarkers that need validation in larger cohorts. Exercise remains the primary therapeutic modality available, and new treatment targets are needed.

Purpose of review: There have been advances in the diagnosis and treatment of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR).

Recent findings: Themes in PMR and GCA include classification criteria, ultrasound imaging of temporal and axillary arteries replacing biopsies for diagnosis of GCA, faster diagnosis and treatment with rapid access clinics for suspected GCA, and expanding treatment options with the goal of rapid suppression of inflammation and sparing steroids.

Summary: Treatment is aimed at suppressing inflammation quickly in both GCA and PMR. Randomized trials have demonstrated success in reducing glucocorticoids when adding advanced therapies such as interleukin 6 (IL6) inhibitors. Other treatments including Janus kinase (JAK) inhibitors (especially a phase 3 trial of upadacitinib at 15 mg daily and secukinumab (an IL17 inhibitor) are being tested. Some uncontrolled GCA protocols are limiting glucocorticoids to initial IV pulse therapy only or rapid tapering of oral glucocorticoids with upfront treatment with tocilizumab. There is uncertainty of who should have an advanced therapy and how long to use it for and what order to consider advanced therapies when treatment fails. In PMR, studies are performed when patients cannot taper glucocorticoids effectively, whereas in GCA, advanced therapies are started with disease onset or with recurrent GCA.

Purpose of review: Over the last 25 years, the role of autologous hematopoietic stem cell transplant (HSCT) in the treatment of diffuse cutaneous systemic sclerosis (dcSSc) has been elucidated. However, multiple critical questions remain regarding this therapy. Of particular interest is the role of HSCT in the treatment of systemic sclerosis (SSc)-associated interstitial lung disease since this is the leading cause of death in SSc.

Recent findings: Most clinical trials and observational studies of HSCT for the treatment of dcSSc have reported pulmonary outcomes as secondary outcomes, Also, most studies have excluded patients with significant pulmonary function impairment. Despite these limitations, there is increasing evidence that suggests that HSCT leads to interstitial lung disease stabilization and possibly improvement of lung function based on pulmonary function tests and imaging.

Summary: HSCT has demonstrated improved long-term outcomes compared to conventional therapies for dcSSC. Future research is needed to refine or expand patient selection, optimize conditioning regimens, and evaluate the potential role of maintenance immunosuppression. We recommend an increased focus on interstitial lung disease since this is the primary cause of death in SSc.

Purpose of review: Systemic vasculitides are characterized by inflammation of blood vessels. Their classification is based on the size of the blood vessels involved - large, medium, or small. Vasculitis early diagnosis and reliable monitoring are crucial to establish a treatment plan and prevent serious complications. Based on these considerations and depending on the location of the affected vessels, the importance of imaging modalities including ultrasonography (US), magnetic resonance Imaging (MRI), magnetic resonance angiography (MRA), computed tomography (CT), computed tomography angiography (CTA), and [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) has progressively increased. In addition to physical exam and laboratory data, these imaging tools offer complementary information about vascular changes occurring in vasculitis.This review summarizes the different imaging modalities being utilized to diagnose and monitor vasculitis.

Recent findings: The most recent update for the use of imaging in vasculitis is referenced in the 2023 European Alliance of Associations for Rheumatology (EULAR) recommendations and the American College of Rheumatology (ACR) guidelines in 2021. Recent advances in PET imaging in large vessel vasculitis include improved technological imaging acquisition and the use of novel radiotracers for cellular and immune targets. FDG-PET has now been demonstrated to have high sensitivity and specificity to detect temporal arteritis.

Summary: Imaging plays a significant role in the evaluation of vasculitis and continues to gain importance in the diagnosis and monitoring of disease activity. Differences exist between the ACR guidelines, which advocates for temporal artery biopsy, and the EULAR guidelines, which favors imaging modalities for the initial evaluation and diagnosis of large vessel vasculitis (LVV). Prerequisites for appropriate clinical management utilizing imaging in patients with vasculitis are the availability and access to skilled clinicians to interpret the images and the cost of these techniques not being prohibitive.